The deployment of vaccine countermeasures against human diseases is currently an issue of critical importance. For example, the following problems have occurred with respect to influenza. Although the proteins hemagglutinin (HA) and neuraminidase (NA) are present on the surface of influenza virus particles, there are 16 types of HA subtypes and 9 types of NA subtypes, and all of these subtypes are present in birds. Among these, highly virulent (highly pathogenic) viruses that kill large numbers of birds are limited to the H5 and H7 subtypes. Influenza caused by a virulent virus having the H5 subtype was first discovered in 1961 in South Africa after spreading among sea birds in the form of the common term. Since then, the virus spread throughout the US in 1983 and 1984, spread to chickens and humans in Hong Kong in 1997, and has since spread throughout all regions of the world. An inactivated whole-virus vaccine for use in humans and chickens has already been developed for the purpose of its prevention. Moreover, the H7 virus, which demonstrates potent virulence in birds, spread throughout the world starting in 1927. It was responsible for a large number of human victims in the Netherlands in the latter half of the 1980s in particular, and after the H7N7 virus had spread to domestic poultry in 2003 as well, it was confirmed to have infected 89 persons and caused 1 death. Subsequent surveys revealed that 59% of persons who had contact with infected poultry were antibody-positive and it is estimated that at least 1,000 people were infected. Moreover, the avian influenza that occurred in China starting in March 2013 also spread to humans, and its cause was determined to be an attenuated strain of the H7N9 subtype.
In addition, hepatitis C virus not only induces symptoms of acute hepatitis through its infection, but also plays a significant negative role in chronic hepatitis and the subsequent onset of cirrhosis and its subsequent escalation to liver cancer. There are two types of viral hepatitis, consisting of that in which infection spreads by oral infection and that which infects through the blood, with the latter being represented by hepatitis B virus and hepatitis C virus. Although vaccines have recently come to be able to be used for hepatitis B virus, with respect to hepatitis C, although there has been considerable progress in the area of chemotherapy, there is still no definitive treatment that is effective against all virus strains, and although research is being aggressively conducted primarily in advanced nations, there is essentially no vaccine that can be provided for practical use.
The causative virus of Japanese encephalitis is a virus that was isolated in Japan in 1935, and there were numerous patients of this disease in Japan at the time. Subsequently, a vaccine inoculation was developed in 1954, after which the number of patients decreased dramatically to the extent that fewer than 10 patients per year have been reported since 1992. However, this does not mean that the virus is no longer present in Japan. Although Japanese encephalitis is thought to infect humans from pigs by being transmitted by mosquitoes, the serum of a large number of pigs in Japan are positive for anti-Japanese encephalitis antibody even at present. In addition, in looking overseas, patients having this disease occur at the rate of 35,000 to 50,000 patients annually, primarily in Asia, with about 10,000 to 15,000 fatalities, thus making this an important infectious disease that requires countermeasures. Inoculation with the vaccine currently used in Japan began in 2009, and is considered to have fewer adverse side-effects than previous vaccines. However, two fatalities from this disease were reported in 2012 in patients who had received inoculations against the disease. In consideration of these circumstances, there is clearly an urgent need to develop a vaccine that is inexpensive and demonstrates few adverse side-effects.
Japan, along with the UK, Australia, New Zealand, Taiwan and Sweden, is one of the exceptional countries where there are no outbreaks of rabies. Outbreaks have occurred in other countries, and these outbreaks cause 30,000 to 50,000 deaths annually. Rabies virus is able to propagate in numerous wild animals, and it is necessary to introduce immunity into wild animals in order to completely prevent rabies. Live vaccines using recombinant vaccinia virus have been effective and are currently attracting attention. However, although problems have yet to be reported at present, the possibility cannot be denied that the wide-ranging introduction of live vaccines into the natural world will lead to unexpected results. Thus, there is a desire for the development of an inexpensive and effective oral inactivated vaccine.
The West Nile virus was first isolated in Uganda in 1935. The infection cycle of this virus exists between birds and mosquitoes and human may occasionally be infected by mosquitoes. Although the rate at which an infected person exhibits symptoms is about 80%, patients with the disease exhibit serious encephalitis and meningitis symptoms at the rate of about 1 in 150 persons, with the disease being fatal in 3% to 15% of serious cases. This disease had not infiltrated the western hemisphere until the occurrence of an outbreak in New York in the summer of 1999. Infected persons have since appeared throughout nearly the entire US, and there is the risk of this disease eventually invading Japan. 36,500 patients have been confirmed in the US during the period from 1999 to 2012, and 1,500 of those patients have died. Mosquitoes already present in Japan are considered to have the ability to transmit this virus, and as such, the entry of this disease into Japan is most likely just a matter of time. Thus, there is an urgent need to develop an effective vaccine.